Mitochondrial DNA haplogroup D4a is a marker for extreme longevity in Japan

Erhan Bilal, Raul Rabadan, Gabriela Alexe, Noriyuki Fuku, Hitomi Ueno, Yutaka Nishigaki, Yasunori Fujita, Masafumi Ito, Yasumichi Arai, Nobuyoshi Hirose, Andrei Ruckenstein, Gyan Bhanot, Masashi Tanaka

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

We report results from the analysis of complete mitochondrial DNA (mtDNA) sequences from 112 Japanese semi-supercentenarians (aged above 105 years) combined with previously published data from 96 patients in each of three non-disease phenotypes: centenarians (99-105 years of age), healthy non-obese males, obese young males and four disease phenotypes, diabetics with and without angiopathy, and Alzheimer's and Parkinson's disease patients. We analyze the correlation between mitochondrial polymorphisms and the longevity phenotype using two different methods. We first use an exhaustive algorithm to identify all maximal patterns of polymorphisms shared by at least five individuals and define a significance score for enrichment of the patterns in each phenotype relative to healthy normals. Our study confirms the correlations observed in a previous study showing enrichment of a hierarchy of haplogroups in the D clade for longevity. For the extreme longevity phenotype we see a single statistically significant signal: a progressive enrichment of certain "beneficial" patterns in centenarians and semi-supercentenarians in the D4a haplogroup. We then use Principal Component Spectral Analysis of the SNP-SNP Covariance Matrix to compare the measured eigenvalues to a Null distribution of eigenvalues on Gaussian datasets to determine whether the correlations in the data (due to longevity) arises from some property of the mutations themselves or whether they are due to population structure. The conclusion is that the correlations are entirely due to population structure (phylogenetic tree). We find no signal for a functional mtDNA SNP correlated with longevity. The fact that the correlations are from the population structure suggests that hitch-hiking on autosomal events is a possible explanation for the observed correlations.

Original languageEnglish
Article numbere2421
JournalPLoS One
Volume3
Issue number6
DOIs
Publication statusPublished - 2008 Jun 11

Fingerprint

Polymorphism
Mitochondrial DNA
Japan
mitochondrial DNA
Phenotype
DNA sequences
phenotype
Single Nucleotide Polymorphism
Covariance matrix
Spectrum analysis
population structure
Population
hiking
genetic polymorphism
couplings
Principal Component Analysis
Parkinson disease
Parkinson Disease
Alzheimer disease
Alzheimer Disease

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Bilal, E., Rabadan, R., Alexe, G., Fuku, N., Ueno, H., Nishigaki, Y., ... Tanaka, M. (2008). Mitochondrial DNA haplogroup D4a is a marker for extreme longevity in Japan. PLoS One, 3(6), [e2421]. https://doi.org/10.1371/journal.pone.0002421

Mitochondrial DNA haplogroup D4a is a marker for extreme longevity in Japan. / Bilal, Erhan; Rabadan, Raul; Alexe, Gabriela; Fuku, Noriyuki; Ueno, Hitomi; Nishigaki, Yutaka; Fujita, Yasunori; Ito, Masafumi; Arai, Yasumichi; Hirose, Nobuyoshi; Ruckenstein, Andrei; Bhanot, Gyan; Tanaka, Masashi.

In: PLoS One, Vol. 3, No. 6, e2421, 11.06.2008.

Research output: Contribution to journalArticle

Bilal, E, Rabadan, R, Alexe, G, Fuku, N, Ueno, H, Nishigaki, Y, Fujita, Y, Ito, M, Arai, Y, Hirose, N, Ruckenstein, A, Bhanot, G & Tanaka, M 2008, 'Mitochondrial DNA haplogroup D4a is a marker for extreme longevity in Japan', PLoS One, vol. 3, no. 6, e2421. https://doi.org/10.1371/journal.pone.0002421
Bilal E, Rabadan R, Alexe G, Fuku N, Ueno H, Nishigaki Y et al. Mitochondrial DNA haplogroup D4a is a marker for extreme longevity in Japan. PLoS One. 2008 Jun 11;3(6). e2421. https://doi.org/10.1371/journal.pone.0002421
Bilal, Erhan ; Rabadan, Raul ; Alexe, Gabriela ; Fuku, Noriyuki ; Ueno, Hitomi ; Nishigaki, Yutaka ; Fujita, Yasunori ; Ito, Masafumi ; Arai, Yasumichi ; Hirose, Nobuyoshi ; Ruckenstein, Andrei ; Bhanot, Gyan ; Tanaka, Masashi. / Mitochondrial DNA haplogroup D4a is a marker for extreme longevity in Japan. In: PLoS One. 2008 ; Vol. 3, No. 6.
@article{484cc8dfb2e04361a463c13d40ee7e6b,
title = "Mitochondrial DNA haplogroup D4a is a marker for extreme longevity in Japan",
abstract = "We report results from the analysis of complete mitochondrial DNA (mtDNA) sequences from 112 Japanese semi-supercentenarians (aged above 105 years) combined with previously published data from 96 patients in each of three non-disease phenotypes: centenarians (99-105 years of age), healthy non-obese males, obese young males and four disease phenotypes, diabetics with and without angiopathy, and Alzheimer's and Parkinson's disease patients. We analyze the correlation between mitochondrial polymorphisms and the longevity phenotype using two different methods. We first use an exhaustive algorithm to identify all maximal patterns of polymorphisms shared by at least five individuals and define a significance score for enrichment of the patterns in each phenotype relative to healthy normals. Our study confirms the correlations observed in a previous study showing enrichment of a hierarchy of haplogroups in the D clade for longevity. For the extreme longevity phenotype we see a single statistically significant signal: a progressive enrichment of certain {"}beneficial{"} patterns in centenarians and semi-supercentenarians in the D4a haplogroup. We then use Principal Component Spectral Analysis of the SNP-SNP Covariance Matrix to compare the measured eigenvalues to a Null distribution of eigenvalues on Gaussian datasets to determine whether the correlations in the data (due to longevity) arises from some property of the mutations themselves or whether they are due to population structure. The conclusion is that the correlations are entirely due to population structure (phylogenetic tree). We find no signal for a functional mtDNA SNP correlated with longevity. The fact that the correlations are from the population structure suggests that hitch-hiking on autosomal events is a possible explanation for the observed correlations.",
author = "Erhan Bilal and Raul Rabadan and Gabriela Alexe and Noriyuki Fuku and Hitomi Ueno and Yutaka Nishigaki and Yasunori Fujita and Masafumi Ito and Yasumichi Arai and Nobuyoshi Hirose and Andrei Ruckenstein and Gyan Bhanot and Masashi Tanaka",
year = "2008",
month = "6",
day = "11",
doi = "10.1371/journal.pone.0002421",
language = "English",
volume = "3",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Mitochondrial DNA haplogroup D4a is a marker for extreme longevity in Japan

AU - Bilal, Erhan

AU - Rabadan, Raul

AU - Alexe, Gabriela

AU - Fuku, Noriyuki

AU - Ueno, Hitomi

AU - Nishigaki, Yutaka

AU - Fujita, Yasunori

AU - Ito, Masafumi

AU - Arai, Yasumichi

AU - Hirose, Nobuyoshi

AU - Ruckenstein, Andrei

AU - Bhanot, Gyan

AU - Tanaka, Masashi

PY - 2008/6/11

Y1 - 2008/6/11

N2 - We report results from the analysis of complete mitochondrial DNA (mtDNA) sequences from 112 Japanese semi-supercentenarians (aged above 105 years) combined with previously published data from 96 patients in each of three non-disease phenotypes: centenarians (99-105 years of age), healthy non-obese males, obese young males and four disease phenotypes, diabetics with and without angiopathy, and Alzheimer's and Parkinson's disease patients. We analyze the correlation between mitochondrial polymorphisms and the longevity phenotype using two different methods. We first use an exhaustive algorithm to identify all maximal patterns of polymorphisms shared by at least five individuals and define a significance score for enrichment of the patterns in each phenotype relative to healthy normals. Our study confirms the correlations observed in a previous study showing enrichment of a hierarchy of haplogroups in the D clade for longevity. For the extreme longevity phenotype we see a single statistically significant signal: a progressive enrichment of certain "beneficial" patterns in centenarians and semi-supercentenarians in the D4a haplogroup. We then use Principal Component Spectral Analysis of the SNP-SNP Covariance Matrix to compare the measured eigenvalues to a Null distribution of eigenvalues on Gaussian datasets to determine whether the correlations in the data (due to longevity) arises from some property of the mutations themselves or whether they are due to population structure. The conclusion is that the correlations are entirely due to population structure (phylogenetic tree). We find no signal for a functional mtDNA SNP correlated with longevity. The fact that the correlations are from the population structure suggests that hitch-hiking on autosomal events is a possible explanation for the observed correlations.

AB - We report results from the analysis of complete mitochondrial DNA (mtDNA) sequences from 112 Japanese semi-supercentenarians (aged above 105 years) combined with previously published data from 96 patients in each of three non-disease phenotypes: centenarians (99-105 years of age), healthy non-obese males, obese young males and four disease phenotypes, diabetics with and without angiopathy, and Alzheimer's and Parkinson's disease patients. We analyze the correlation between mitochondrial polymorphisms and the longevity phenotype using two different methods. We first use an exhaustive algorithm to identify all maximal patterns of polymorphisms shared by at least five individuals and define a significance score for enrichment of the patterns in each phenotype relative to healthy normals. Our study confirms the correlations observed in a previous study showing enrichment of a hierarchy of haplogroups in the D clade for longevity. For the extreme longevity phenotype we see a single statistically significant signal: a progressive enrichment of certain "beneficial" patterns in centenarians and semi-supercentenarians in the D4a haplogroup. We then use Principal Component Spectral Analysis of the SNP-SNP Covariance Matrix to compare the measured eigenvalues to a Null distribution of eigenvalues on Gaussian datasets to determine whether the correlations in the data (due to longevity) arises from some property of the mutations themselves or whether they are due to population structure. The conclusion is that the correlations are entirely due to population structure (phylogenetic tree). We find no signal for a functional mtDNA SNP correlated with longevity. The fact that the correlations are from the population structure suggests that hitch-hiking on autosomal events is a possible explanation for the observed correlations.

UR - http://www.scopus.com/inward/record.url?scp=48749085727&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=48749085727&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0002421

DO - 10.1371/journal.pone.0002421

M3 - Article

C2 - 18545700

AN - SCOPUS:48749085727

VL - 3

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e2421

ER -